HEPATIC ORGANIC ANION UPTAKE AND TRANSPORT

Project: Research project

Project Details

Description

Uptake of organic anions by the liver has kinetic characteristics of
carrier-mediated transport. In previous studies an organic anion binding
protein (OABP) from a sinusoidal-enriched rat liver cell plasma membrane
subfraction was identified and purified. Monospecific antibodies raised to
OABP have permitted its quantitation by ELISA and its detection by
immunoblotting. Studies of liver distribution by immunocytochemistry
reveal that OABP is limited to the sinusoidal and lateral surface membrane
of the hepatocyte. There is no reactivity seen in canaliculi, within cells
or in different cell types. Several model systems in which organic anion
transport and OABP concentration are reduced have been described (e.g.
development, regeneration), and studies of BSP transport have been extended
to short-term cultured rat hepatocytes. These cells are easily manipulated
and permit studies of liver cell transport without the hemodynamic and
hormonal alterations which may complicate studies performed in intact
animals. The long-term goal is to understand the mechanism of organic
anion transport and its relationship to specific proteins in normal liver
and in various acquired and inheritable disorders. The specific aims are
to: (1) Define saturation kinetics, temperature dependence, and
specificity of BSP transport in short-term cultured hepatocytes from normal
rats and from rats in which BSP uptake is reduced (e.g. regeneration,
nafenopin treatment) and to study the potential function of OABP in these
cells by the preparation and use of specific radiolabeled affinity probes;
(2) Prepare cDNA probes for OABP from phage liver libraries screened with
anti-OABP or oligonucleotide probes synthesized according to the sequence
of CNBr peptide fragments of OABP. These probes will permit studies of
regulation of OABP expression and also permit sequencing of OABP to
determine identity or areas of homology with known proteins; and (3) Study
cellular and subcellular distribution of OABP by immunocytochemistry in
liver, cultured hepatocytes, and other organs that contain OABP and
transport organic anions (heart, brain, kidney, and GI tract).
StatusFinished
Effective start/end date1/1/901/1/90

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases

ASJC

  • Biophysics
  • Transportation
  • Histology
  • Hepatology
  • Pharmaceutical Science

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